Multiple Subtypes of Ca2+ Currents Contribute to the Spontaneous Regenerative Activities in Mammalian Retinal Bipolar Cells

Abstract

Abstract: : Purpose: To characterize the regenerative spontaneous activities and the underlying ionic mechanisms in mammalian retinal bipolar cells. Method: Patch-clamp recordings in whole-cell or perforated configurations were performed on acutely isolated retinal bipolar cells from ≥4-week-old rats. Intracellular Ca₂₊ concentrations were monitored by using Ca₂₊-sensitive dyes. Results: Under current-clamp with no or a small negative holding current (<-10 pA), isolated bipolar cells exhibit regular, spontaneous regenerative activities from a relative stable membrane potential around -80 mV. The shape and duration of the spontaneous waveforms for each cell are remarkably similar and could also be evoked by a brief depolarizing current. The waveforms, however, were found to be different between rod and cone bipolar cells. The spontaneous activities were also observed in the isolated axon terminals as well as in the isolated somas from rod bipolar cells. The latter are known to lack L-type Ca₂₊ currents. The spontaneous activities were accompanied by intracellular Ca₂₊ transients. The waveforms were reduced by nimodipine and enhanced by Bay K-8644. Blockade of potential Ca₂₊-induced Ca₂₊ release was not found to affect significantly the spontaneous activities or the waveforms. Application of mibefradil, a T-type Ca₂₊ channels antagonist, or Co₂₊ blocked the spontaneous activity. Conclusion: Isolated mammalian retinal rod and cone bipolar cells exhibit regenerative activities with distinct waveforms. The regenerative activities are triggered by T-type Ca₂₊ currents and the response waveforms are shaped by L-type Ca₂₊ currents. Both T- and L-type Ca₂₊ currents contribute to the regenerative property of mammalian bipolar cells.

Keywords: 330 bipolar cells • 334 calcium • 555 retina: distal(photoreceptors, horizontal cells, bipolar cells)